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MKSAP Quiz: 3-day history of left knee pain, swelling

A 43-year-old woman is evaluated for a 3-day history of left knee pain and swelling. Similar episodes have occurred in either knee as well as the left wrist during the past 2 years. Following a physical exam, radiographs, and joint aspiration of the left knee, what laboratory study will most likely identify the cause of this patient's symptoms?


A 43-year-old woman is evaluated for a 3-day history of left knee pain and swelling. Similar episodes have occurred in either knee as well as the left wrist during the past 2 years. She also reports a sense of generalized weakness, and has experienced constipation and vague abdominal discomfort during the past year. Because of her constipation, her thyroid-stimulating hormone level was recently measured and found to be normal. She takes no medications.

On physical examination, vital signs are normal. The left knee is warm with a moderate- to large-sized effusion, and decreased range of motion is noted. Proximal muscle strength is normal.

Radiographs show a thin white line at the chondral surfaces of both knees and at the pubic symphysis.

Joint aspiration of the left knee shows a leukocyte count of 35,000/µL (35 × 109/L), with 90% neutrophils; polarizing microscopy shows numerous positively birefringent rhomboid crystals within neutrophils.

Which of the following laboratory studies will most likely identify the cause of this patient's symptoms?

A. Anti–cyclic citrullinated peptide antibodies
B. Serum calcium
C. Serum creatine kinase
D. Serum urate

Reveal the Answer

MKSAP Answer and Critique

The correct answer is B. Serum calcium. This content is available to MKSAP 18 subscribers as Question 28 in the Rheumatology section. More information about MKSAP is available online.

A serum calcium measurement is most likely to identify the cause of this patient's symptoms. This young woman has recurrent attacks of acute calcium pyrophosphate (CPP) crystal arthritis (pseudogout). Clues to the diagnosis include acute and recurrent self-limited monoarticular arthritis, chondrocalcinosis on radiograph, and, most tellingly, identification of CPP crystals under polarizing microscopy. This condition usually affects the elderly; therefore, evidence of acute CPP crystal arthritis in a young person should always prompt an investigation for secondary causes. Secondary causes include hyperparathyroidism, hypothyroidism, hypophosphatasia, hypomagnesemia, and hemochromatosis. This patient has recent-onset signs and symptoms suggestive of hypercalcemia and hyperparathyroidism, including abdominal discomfort, constipation, and weakness. Therefore, measuring the serum calcium is appropriate (and serum parathyroid hormone, if hypercalcemia is present), because this patient appears to have CPP deposition due to hyperparathyroidism.

Anti–cyclic citrullinated peptide antibodies are useful in the diagnosis of rheumatoid arthritis (RA). RA typically presents with the insidious onset of symmetric arthritis in the hands and feet along with morning stiffness. Monoarthritis is a rare presenting feature of RA, but it is usually followed by development of the symmetric arthritis.

Checking serum creatine kinase would not be a first-line test for this patient. Although muscle disease is associated with weakness, myositis would not account for many of the other manifestations, including the monoarticular arthritis, radiographic chondrocalcinosis, and synovial fluid crystals.

Serum urate would be an appropriate laboratory study to measure if gout was suspected, but the synovial fluid analysis is consistent with acute CPP crystal arthritis rather than gout, in which negatively birefringent crystals are seen. Gout also more typically affects the metatarsophalangeal joints, the mid foot, ankles, and knees, although the finger joints may be affected in postmenopausal women.

Key Point

  • Evidence of acute calcium pyrophosphate crystal arthritis (pseudogout) in a young person should always prompt an investigation for secondary causes such as hyperparathyroidism, hypothyroidism, hypophosphatasia, hypomagnesemia, and hemochromatosis.